Newly developed techniques in nuclear magnetic resonance spectroscopy (NMR) of 1H, 13C and 31p will be used to investigate normal and disordered cerebral metabolism in living human subjects. Collectively, these non-invasive methods are a means of making repeated measurements of specific compounds in functioning nervous tissue in a manner comparable to biopsy, but without tissue damage or agonal change. The measurements, which will be made directly in various parts of the brain are of the relative concentrations of phosphocreatine, adenosine triphosphate, inorganic phosphate, intracellular pH, pools of mono- and diesters of phosphoric acid, elevated lactate, N-acetylaspartate, pools of compounds containing choline and creatine, and some concentrated amino acids. The work will be done in a newly designed 2.3 Tesla Oxford/Bruker spectrometer with water proton imaging capability; this instrument will be the first of its kind. Following a short series of experiments on dogs to adapt established spectrometer techniques to the larger machine, standard procedures for human recording will be developed and determination of the characteristics and variation of normal spectra begun. A major effort will be made to localize the source of spectral signals within the brain by a combination of advanced spectroscopic techniques. Patients with dementia and multiple sclerosis will then be studied to gain new information about the biochemistry of neurons and glia in gray and white matter in which the proportions of these cell types have been altered by disease. Patients with complex partial seizures being considered for temporal lobectomy, patients with or at risk for stroke, and patients with brain tumors will be studied to evaluate NMR-measureeable quantities as predictors of outcome and adjuncts to management.